Altered hepatic metabolic landscape and insulin sensitivity in response to pulmonary tuberculosis.

Chronic inflammation triggers development of metabolic disease, and pulmonary tuberculosis (TB) generates chronic systemic inflammation. Whether TB induced-inflammation impacts metabolic organs and leads to metabolic disorder is ill defined. The liver is the master regulator of metabolism and to determine the impact of pulmonary TB on this organ we undertook an unbiased mRNA and protein analyses of the liver in mice with TB and reanalysed published data on human disease. Pulmonary TB led to upregulation of genes in the liver related to immune signalling and downregulation of genes encoding metabolic processes. In liver, IFN signalling pathway genes were upregulated and this was reflected in increased biochemical evidence of IFN signalling, including nuclear location of phosphorylated Stat-1 in hepatocytes. The liver also exhibited reduced expression of genes encoding the gluconeogenesis rate-limiting enzymes Pck1 and G6pc. Phosphorylation of CREB, a transcription factor controlling gluconeogenesis was drastically reduced in the livers of mice with pulmonary TB as was phosphorylation of other glucose metabolism-related kinases, including GSK3a, AMPK, and p42. In support of the upregulated IFN signalling being linked to the downregulated metabolic functions in the liver, we found suppression of gluconeogenic gene expression and reduced CREB phosphorylation in hepatocyte cell lines treated with interferons. The impact of reduced gluconeogenic gene expression in the liver was seen when infected mice were less able to convert pyruvate, a gluconeogenesis substrate, to the same extent as uninfected mice. Infected mice also showed evidence of reduced systemic and hepatic insulin sensitivity. Similarly, in humans with TB, we found that changes in a metabolite-based signature of insulin resistance correlates temporally with successful treatment of active TB and with progression to active TB following exposure. These data support the hypothesis that TB drives interferon-mediated alteration of hepatic metabolism resulting in reduced gluconeogenesis and drives systemic reduction of insulin sensitivity.

Device-measured physical activity and cardiac structure by magnetic resonance.

BACKGROUND AND AIMS: Although extreme cardiac adaptions mirroring phenotypes of cardiomyopathy have been observed in endurance athletes, adaptions to high levels of physical activity within the wider population are under-explored. Therefore, in this study, associations between device-measured physical activity and clinically relevant cardiac magnetic resonance volumetric indices were investigated. METHODS: Individuals without known cardiovascular disease or hypertension were included from the UK Biobank. Cardiac magnetic resonance data were collected between 2015 and 2019, and measures of end-diastolic chamber volume, left ventricular (LV) wall thickness, and LV ejection fraction were extracted. Moderate-to-vigorous-intensity physical activity (MVPA), vigorous-intensity physical activity (VPA), and total physical activity were assessed via wrist-worn accelerometers. RESULTS: A total of 5977 women (median age and MVPA: 62 years and 46.8 min/day, respectively) and 4134 men (64 years and 49.8 min/day, respectively) were included. Each additional 10 min/day of MVPA was associated with a 0.70 [95% confidence interval (CI): 0.62, 0.79] mL/m2 higher indexed LV end-diastolic volume (LVEDVi) in women and a 1.08 (95% CI: 0.95, 1.20) mL/m2 higher LVEDVi in men. However, even within the top decile of MVPA, LVEDVi values remained within the normal ranges [79.1 (95% CI: 78.3, 80.0) mL/m2 in women and 91.4 (95% CI: 90.1, 92.7) mL/m2 in men]. Associations with MVPA were also observed for the right ventricle and the left/right atria, with an inverse association observed for LV ejection fraction. Associations of MVPA with maximum or average LV wall thickness were not clinically meaningful. Results for total physical activity and VPA mirrored those for MVPA. CONCLUSIONS: High levels of device-measured physical activity were associated with cardiac remodelling within normal ranges.

Joint associations of diet and physical activity with incident type 2 diabetes and hypertension: an analysis of 144,288 UK Biobank participants.

BACKGROUND: Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of UK adults. METHODS: This prospective cohort study included 144,288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorised PA and diet indicators (diet quality score (DQS) and energy intake (EI)) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). RESULTS: A total of 14,003(7.1%) participants developed T2D, 28,075(19.2%) developed hypertension, and 30,529(21.2%) developed T2D or hypertension over a mean follow-up of 10.9(3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet, e.g. among high DQS group, hazard ratios in middle and high MVPA group were 0.90 (95%CI:0.86-0.94), and 0.88(95%CI:0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR: 0.84, 95%CI:0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. CONCLUSION: Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.

Twenty-four-hour physical behaviour profiles across type 2 diabetes mellitus subtypes.

AIM: To investigate how 24-h physical behaviours differ across type 2 diabetes (T2DM) subtypes. MATERIALS AND METHODS: We included participants living with T2DM, enrolled as part of an ongoing observational study. Participants wore an accelerometer for 7 days to quantify physical behaviours across 24 h. We used routinely collected clinical data (age at onset of diabetes, glycated haemoglobin level, homeostatic model assessment index of beta-cell function, homeostatic model assessment index of insulin resistance, body mass index) to replicate four previously identified subtypes (insulin-deficient diabetes [INS-D], insulin-resistant diabetes [INS-R], obesity-related diabetes [OB] and age-related diabetes [AGE]), via k-means clustering. Differences in physical behaviours across the diabetes subtypes were assessed using generalized linear models, with the AGE cluster as the reference. RESULTS: A total of 564 participants were included in this analysis (mean age 63.6 ± 8.4 years, 37.6% female, mean age at diagnosis 53.1 ± 10.0 years). The proportions in each cluster were as follows: INS-D: n = 35, 6.2%; INS-R: n = 88, 15.6%; OB: n = 166, 29.4%; and AGE: n = 275, 48.8%. Compared to the AGE cluster, the OB cluster had a shorter sleep duration (-0.3 h; 95% confidence interval [CI] -0.5, -0.1), lower sleep efficiency (-2%; 95% CI -3, -1), lower total physical activity (-2.9 mg; 95% CI -4.3, -1.6) and less time in moderate-to-vigorous physical activity (-6.6 min; 95% CI -11.4, -1.7), alongside greater sleep variability (17.9 min; 95% CI 8.2, 27.7) and longer sedentary time (31.9 min; 95% CI 10.5, 53.2). Movement intensity during the most active continuous 10 and 30 min of the day was also lower in the OB cluster. CONCLUSIONS: In individuals living with T2DM, the OB subtype had the lowest levels of physical activity and least favourable sleep profiles. Such behaviours may be suitable targets for personalized therapeutic lifestyle interventions.

Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

AIMS: To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol-1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol-1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6-week interventions: (1) exercise training (EX; 70%-75% maximum heart rate; four sessions/week; n = 13) or (2) non-exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA-IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin-18 (CK18) M65, among others. RESULTS: In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA-IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = -0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). CONCLUSIONS: Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate-intensity exercise training.

Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. METHODS: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. RESULTS: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. CONCLUSION: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. TRIAL REGISTRATION: NCT02590822.

Sarcopenia prevalence using handgrip strength or chair stand performance in adults living with type 2 diabetes mellitus.

BACKGROUND: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. OBJECTIVE: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. METHODS: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. RESULTS: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. CONCLUSIONS: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.

Long-term ambient air pollution exposure and prospective change in sedentary behaviour and physical activity in individuals at risk of type 2 diabetes in the UK.

BACKGROUND: Air pollution may be a risk factor for physical inactivity and sedentary behaviour (SED) through discouraging active lifestyles, impairing fitness and contributing to chronic diseases with potentially important consequences for population health. METHODS: Using generalized estimating equations, we examined the associations between long-term particulate matter with diameter ≤2.5 µm (PM2.5), ≤10 µm (PM10) and nitrogen dioxide (NO2) and annual change in accelerometer-measured SED, moderate-to-vigorous physical activity (MVPA) and steps in adults at risk of type 2 diabetes within the Walking Away from Type 2 Diabetes trial. We adjusted for important confounders including social deprivation and measures of the built environment. RESULTS: From 808 participants, 644 had complete data (1605 observations; 64.7% men; mean age 63.86 years). PM2.5, NO2 and PM10 were not associated with change in MVPA/steps but were associated with change in SED, with a 1 ugm-3 increase associated with 6.38 (95% confidence interval: 0.77, 12.00), 1.52 (0.49, 2.54) and 4.48 (0.63, 8.34) adjusted annual change in daily minutes, respectively. CONCLUSIONS: Long-term PM2.5, NO2 and PM10 exposures were associated with an annual increase in SED: ~11-22 min/day per year across the sample range of exposure (three standard deviations). Future research should investigate whether interventions to reduce pollution may influence SED.

Associations of objectively measured physical activity, sedentary time and cardiorespiratory fitness with adipose tissue insulin resistance and ectopic fat.

BACKGROUND/OBJECTIVES: Inadequate movement, excess adiposity, and insulin resistance augment cardiometabolic risk. This study examined the associations of objectively measured moderate-to-vigorous intensity physical activity (MVPA), sedentary time and cardiorespiratory fitness (CRF), with adipose tissue insulin resistance and ectopic fat. METHODS: Data were combined from two previous experimental studies with community volunteers (n = 141, male = 60%, median (interquartile range) age = 37 (19) years, body mass index (BMI) = 26.1 (6.3) kg·m-2). Adipose tissue insulin resistance was assessed using the adipose tissue insulin resistance index (Adipo-IR); whilst magnetic resonance imaging (MRI) was used to measure liver, visceral (VAT) and subcutaneous abdominal adipose tissue (ScAT). Sedentary time and MVPA were measured via an ActiGraph GT3X+ accelerometer. Generalized linear models examined the association of CRF, MVPA, and sedentary time with Adipo-IR and fat depots. Interaction terms explored the moderating influence of age, sex, BMI and CRF. RESULTS: After controlling for BMI and cardiometabolic variables, sedentary time was positively associated with Adipo-IR (ß = 0.68 AU [95%CI = 0.27 to 1.10], P < 0.001). The association between sedentary time and Adipo-IR was moderated by age, CRF and BMI; such that it was stronger in individuals who were older, had lower CRF and had a higher BMI. Sedentary time was also positively associated with VAT (ß = 0.05 L [95%CI = 0.01 to 0.08], P = 0.005) with the relationship being stronger in females than males. CRF was inversely associated with VAT (ß = -0.02 L [95%CI = -0.04 to -0.01], P = 0.003) and ScAT (ß = -0.10 L [95%CI = -0.13 to -0.06], P < 0.001); with sex and BMI moderating the strength of associations with VAT and ScAT, respectively. CONCLUSIONS: Sedentary time is positively associated with adipose tissue insulin resistance which regulates lipogenesis and lipolysis. CRF is independently related to central fat storage which is a key risk factor for cardiometabolic disease.

Impact of novel glucose-lowering therapies on physical function in people with type 2 diabetes: A systematic review and meta-analysis of randomised placebo-controlled trials.

AIMS: We investigated evidence from randomised, placebo-controlled trials of novel glucose-lowering therapies; sodium-glucose co-transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), on physical function in people with type 2 diabetes (T2D). METHODS: PubMed, Medline, Embase and Cochrane library were searched from 1 April 2005 to 20 January 2022. The primary outcome was change in physical function in groups receiving a novel glucose-lowering therapy versus placebo at the trial end-point. RESULTS: Eleven studies met our criteria including nine for GLP-1RA and one each for SGLT2i and DPP4i. Eight studies included a self-reported measure of physical function, seven with GLP-1RA. Pooled meta-analysis showed an improvement of 0.12 (0.07, 017) points in favour of novel glucose-lowering therapies, mainly GLP-1RA. These findings were consistent when assessed individually for commonly used subjective assessments of physical function; namely the Short-Form 36 item-questionnaire (SF-36; all investigating GLP-1RA) and the Impact of Weight on Quality of Life-Lite (IWQOL-LITE; all, except one, exploring GLP-1RA) with estimated treatment differences (ETDs) of 0.86 (0.28, 1.45) and 3.72 (2.30, 5.15) respectively in favour of novel GLTs. For objective measures of physical function (VO2max and 6-minute walk test (6MWT)) no significant between-group differences between the intervention and the placebo were found. CONCLUSIONS: GLP-1RAs showed improvements in self-reported outcomes of physical function. However, there is limited evidence to draw definitive conclusions especially because of lack of studies exploring the impact of SGLT2i and DPP4i on physical function. There is a need for dedicated trials to establish the association between novel agents and physical function.

Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.

Participant and workplace champion experiences of an intervention designed to reduce sitting time in desk-based workers: SMART work & life.

BACKGROUND: A cluster randomised controlled trial demonstrated the effectiveness of the SMART Work & Life (SWAL) behaviour change intervention, with and without a height-adjustable desk, for reducing sitting time in desk-based workers. Staff within organisations volunteered to be trained to facilitate delivery of the SWAL intervention and act as workplace champions. This paper presents the experiences of these champions on the training and intervention delivery, and from participants on their intervention participation. METHODS: Quantitative and qualitative feedback from workplace champions on their training session was collected. Participants provided quantitative feedback via questionnaires at 3 and 12 month follow-up on the intervention strategies (education, group catch ups, sitting less challenges, self-monitoring and prompts, and the height-adjustable desk [SWAL plus desk group only]). Interviews and focus groups were also conducted at 12 month follow-up with workplace champions and participants respectively to gather more detailed feedback. Transcripts were uploaded to NVivo and the constant comparative approach informed the analysis of the interviews and focus groups. RESULTS: Workplace champions rated the training highly with mean scores ranging from 5.3/6 to 5.7/6 for the eight parts. Most participants felt the education increased their awareness of the health consequences of high levels of sitting (SWAL: 90.7%; SWAL plus desk: 88.2%) and motivated them to change their sitting time (SWAL: 77.5%; SWAL plus desk: 85.77%). A high percentage of participants (70%) reported finding the group catch up session helpful and worthwhile. However, focus groups highlighted mixed responses to the group catch-up sessions, sitting less challenges and self-monitoring intervention components. Participants in the SWAL plus desk group felt that having a height-adjustable desk was key in changing their behaviour, with intrinsic as well as time based factors reported as key influences on the height-adjustable desk usage. In both intervention groups, participants reported a range of benefits from the intervention including more energy, less fatigue, an increase in focus, alertness, productivity and concentration as well as less musculoskeletal problems (SWAL plus desk group only). Work-related, interpersonal, personal attributes, physical office environment and physical barriers were identified as barriers when trying to sit less and move more. CONCLUSIONS: Workplace champion and participant feedback on the intervention was largely positive but it is clear that different behaviour change strategies worked for different people indicating that a 'one size fits all' approach may not be appropriate for this type of intervention. The SWAL intervention could be tested in a broader range of organisations following a few minor adaptations based on the champion and participant feedback. TRIAL REGISTRATION: ISCRCTN registry (ISRCTN11618007).

Life expectancy following a cardiovascular event in individuals with and without type 2 diabetes: A UK multi-ethnic population-based observational study.

BACKGROUND AND AIMS: We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity. METHODS AND RESULTS: We used the Clinical Practice Research Datalink database in England (UK), linked to the Hospital Episode Statistics information, to identify individuals with and without T2D who survived a first CVD event between 1st Jan 2007 and 31st Dec 2017; subsequent death events were extracted from the Office for National Statistics database. Ethnicity was categorised as White, South Asian (SA), Black, or other. Flexible parametric survival models were used to estimate survival and predict life expectancy. 59,939 individuals with first CVD event were included: 7596 (12.7%) with T2D (60.9% men; mean age at event: 69.7 years [63.2 years in SA, 65.9 in Black, 70.2 in White]) and 52,343 without T2D (56.7% men; 65.9 years [54.7 in Black, 58.2 in SA, 66.3 in White]). Accounting for potential confounders (sex, deprivation, lipid-lowering medication, current smoking, and pre-existing hypertension), comparing individuals with vs without T2D the mortality rate was 53% higher in White (hazard ratio [HR]: 1.53 [95% CI: 1.44, 1.62]), corresponding to a potential loss of 3.87 (3.30, 4.44) life years at the age of 50 years in individuals with T2D. No evidence of a difference in life expectancy was observed in individuals of SA (HR: 0.82 [0.52, 1.29]; -1.36 [-4.58, 1.86] life years), Black (HR: 1.26 [0.59, 2.70]; 1.21 [-2.99, 5.41] life years); and other (HR: 1.64 [0.80, 3.39]; 3.89 [-2.28, 9.99] life years) ethnic group. CONCLUSION: Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups.

The effect of acute and chronic exercise on hepatic lipid composition.

Exercise is recommended for those with, or at risk of nonalcoholic fatty liver disease (NAFLD), owing to beneficial effects on hepatic steatosis and cardiometabolic risk. Whilst exercise training reduces total intrahepatic lipid in people with NAFLD, accumulating evidence indicates that exercise may also modulate hepatic lipid composition. This metabolic influence is important as the profile of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) dramatically affect the metabolic consequences of hepatic lipid accumulation; with SFA being especially lipotoxic. Relatedly, obesity and NAFLD are associated with hepatic PUFA depletion and elevated SFA. This review summarizes the acute (single bout) and chronic (exercise training) effects of exercise on hepatic lipid composition in rodents (acute studies: n = 3, chronic studies: n = 13) and humans (acute studies: n = 1, chronic studies: n = 3). An increased proportion of hepatic PUFA after acute and chronic exercise is the most consistent finding of this review. Mechanistically, this may relate to an enhanced uptake of adipose-derived PUFA (reflecting habitual diet), particularly in rodents. A relative decrease in the proportion of hepatic MUFA after chronic exercise is also documented repeatedly, particularly in rodent models with elevated hepatic MUFA. This outcome is related to decreased hepatic stearoyl-CoA desaturase-1 activity in some studies. Findings regarding hepatic SFA are less consistent and limited by the absence of metabolic challenge in rodent models. These findings require confirmation in well-controlled interventions in people with NAFLD. These studies will be facilitated by recently validated magnetic resonance spectroscopy techniques, able to precisely quantify hepatic lipid composition in vivo.

COVID-19 vaccination uptake amongst ethnic minority communities in England: a linked study exploring the drivers of differential vaccination rates.

BACKGROUND: Despite generally high coronavirus disease 2019 (COVID-19) vaccination rates in the UK, vaccination hesitancy and lower take-up rates have been reported in certain ethnic minority communities. METHODS: We used vaccination data from the National Immunisation Management System (NIMS) linked to the 2011 Census and individual health records for subjects aged ≥40 years (n = 24 094 186). We estimated age-standardized vaccination rates, stratified by ethnic group and key sociodemographic characteristics, such as religious affiliation, deprivation, educational attainment, geography, living conditions, country of birth, language skills and health status. To understand the association of ethnicity with lower vaccination rates, we conducted a logistic regression model adjusting for differences in geographic, sociodemographic and health characteristics. ResultsAll ethnic groups had lower age-standardized rates of vaccination compared with the white British population, whose vaccination rate of at least one dose was 94% (95% CI: 94%-94%). Black communities had the lowest rates, with 75% (74-75%) of black African and 66% (66-67%) of black Caribbean individuals having received at least one dose. The drivers of these lower rates were partly explained by accounting for sociodemographic differences. However, modelled estimates showed significant differences remained for all minority ethnic groups, compared with white British individuals. CONCLUSIONS: Lower COVID-19 vaccination rates are consistently observed amongst all ethnic minorities.

Sedentary behaviour and disease risk.

Sedentary behaviour has become the new reference of living, which has paralleled the increase in the prevalence of multiple chronic diseases. Here, we highlight the evidence to date and propose specific topics of interest for the Collection at BMC Public Health, titled "Sedentary behaviour and disease risk".

Self-reported walking pace: A simple screening tool with lowest risk of all-cause mortality in those that 'walk the talk'.

To determine whether the association between self-reported walking pace and all-cause mortality (ACM) persists across categories of accelerometer-assessed physical activity status. Data from 93,709 UK Biobank participants were included. Physical activity was assessed using wrist-worn accelerometers for 7-days. Participants accumulating <150 min/week moderate-to-vigorous- activity were classed as "inactive", ≥150 min/week moderate (≥3 METs) activity as "somewhat active" excluding those with ≥150 min/week upper-moderate-to-vigorous activity (≥4.3 METs), who were classed as "high-active". Over a 6.3 y (median) follow-up, 2,173 deaths occurred. More than half of slow walkers were "inactive", but only 26% of steady and 12% of brisk walkers. Associations between walking pace and ACM were consistent with those for activity. "High active" brisk walkers had the lowest risk of ACM (Hazard Ratio (HR) 0.22; 95% CI: 0.17,0.28), relative to "inactive" slow walkers. Within those classed as "inactive", steady (HR 0.54; 0.46,0.64) and brisk walkers (HR 0.42; 0.34,0.52) had lower risk than slow walkers. In conclusion, self-reported walking pace was associated with accelerometer-assessed physical activity with both exposures having similar associations with ACM. "inactive", steady, and brisk walkers had lower ACM risk than slow walkers. The pattern was similar for "High active" participants. Overall, "High active" brisk walkers had lowest risk.

Accelerometer-Assessed Physical Activity in People with Type 2 Diabetes: Accounting for Sleep when Determining Associations with Markers of Health.

High physical activity levels during wake are beneficial for health, while high movement levels during sleep are detrimental to health. Our aim was to compare the associations of accelerometer-assessed physical activity and sleep disruption with adiposity and fitness using standardized and individualized wake and sleep windows. People (N = 609) with type 2 diabetes wore an accelerometer for up to 8 days. Waist circumference, body fat percentage, Short Physical Performance Battery (SPPB) test score, sit-to-stands, and resting heart rate were assessed. Physical activity was assessed via the average acceleration and intensity distribution (intensity gradient) over standardized (most active 16 continuous hours (M16h)) and individualized wake windows. Sleep disruption was assessed via the average acceleration over standardized (least active 8 continuous hours (L8h)) and individualized sleep windows. Average acceleration and intensity distribution during the wake window were beneficially associated with adiposity and fitness, while average acceleration during the sleep window was detrimentally associated with adiposity and fitness. Point estimates for the associations were slightly stronger for the standardized than for individualized wake/sleep windows. In conclusion, standardized wake and sleep windows may have stronger associations with health due to capturing variations in sleep durations across individuals, while individualized windows represent a purer measure of wake/sleep behaviors.

The effectiveness of the Structured Health Intervention For Truckers (SHIFT): a cluster randomised controlled trial (RCT).

BACKGROUND: Long distance heavy goods vehicle (HGV) drivers exhibit higher than nationally representative rates of obesity, and obesity-related co-morbidities, and are underserved in terms of health promotion initiatives. The purpose of this study was to evaluate the effectiveness of the multicomponent 'Structured Health Intervention For Truckers' (SHIFT), compared to usual care, at 6- and 16-18-month follow-up. METHODS: We conducted a two-arm cluster RCT in transport sites throughout the Midlands, UK. Outcome measures were assessed at baseline, at 6- and 16-18-month follow-up. Clusters were randomised (1:1) following baseline measurements to either the SHIFT arm or usual practice control arm. The 6-month SHIFT programme included a group-based interactive 6-h education and behaviour change session, health coach support and equipment provision (Fitbit® and resistance bands/balls to facilitate a 'cab workout'). The primary outcome was device-assessed physical activity (mean steps/day) at 6 months. Secondary outcomes included the following: device-assessed sitting, physical activity intensity and sleep; cardiometabolic health, diet, mental wellbeing and work-related psychosocial variables. Data were analysed using mixed-effect linear regression models using a complete-case population. RESULTS: Three hundred eighty-two HGV drivers (mean ± SD age: 48.4 ± 9.4 years, BMI: 30.4 ± 5.1 kg/m2, 99% male) were recruited across 25 clusters (sites) and randomised into either the SHIFT (12 clusters, n = 183) or control (13 clusters, n = 199) arms. At 6 months, 209 (55%) participants provided primary outcome data. Significant differences in mean daily steps were found between groups, in favour of the SHIFT arm (adjusted mean difference: 1008 steps/day, 95% CI: 145-1871, p = 0.022). Favourable differences were also seen in the SHIFT group, relative to the control group, in time spent sitting (- 24 mins/day, 95% CI: - 43 to - 6), and moderate-to-vigorous physical activity (6 mins/day, 95% CI: 0.3-11). Differences were not maintained at 16-18 months. No differences were observed between groups in the other secondary outcomes at either follow-up. CONCLUSIONS: The SHIFT programme led to a potentially clinically meaningful difference in daily steps, between trial arms, at 6 months. Whilst the longer-term impact is unclear, the programme offers potential to be incorporated into driver training courses to promote activity in this at-risk, underserved and hard-to-reach essential occupational group. TRIAL REGISTRATION: ISRCTN10483894 (date registered: 01/03/2017).

Effect of high-pain versus low-pain structured exercise on walking ability in people with intermittent claudication: meta-analysis.

BACKGROUND: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC). METHODS: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms-structured low-pain exercise, structured high--pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome. RESULTS: Some 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, -0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA. CONCLUSION: There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).